Interesting op-ed piece by Dr. Barron H. Lerner, Professor of Medicine at NYU, in the NY Times titled “Overruling My Father”. Dr. Lerner describes his own experience with his father, an infectious disease physician, who had progressive Parkinson’s disease and was in a nursing home. As his condition worsened the family including Dr. Lerner didn’t want to escalate care although his father expressed wanting to pursue aggressive measures. Check out the article below!
- Lymphoproliferative disorder which is histologically characterized by angiofollicular lymph-node hypertrophy.
- In the differential diagnosis for localized/diffuse lymphadenopathy with or without systemic manifestations.
- Rare and relatively benign disorder which can mimick lymphoma clinically, but varies from the latter histologically, prognostically and in its treatment options.
- Localized CD:
- By definition, localized to one site.
- Features lymphoid hyperplasia associated with excessive angiogenesis.
- Asymptomatic in over 50% of patients and is often discovered incidentally.
- Histological diagnosis requires lymph-node biopsy.
- Multicentric CD:
- Characterized by a predominantly lymphadenopathic presentation consistently involving peripheral lymph-nodes and manifestations of multisystem involvement.
- Considered as a systemic B cell lymphoproliferation, probably arising in immunoregulatory deficit, and resulting in the outgrowth of clonal B-cell populations.
- It is always symptomatic.
- Symptoms, primarily a consequence of elevated Interleukin-6 (IL-6) production, are:
- Weight loss(67%)
- Polyadenopathy is common with a mean of four sites involved and is often associated with hepatosplenomegaly.
- Histological diagnosis is made upon biopsy of an excised peripheral lymph-node.
- Other forms/associations:
- A POEMS (Peripheral polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy(M-Protein) and Skin signs) syndrome is observed in 24% of patients.
- Some MCD forms are associated with Kaposi’s sarcoma displaying prominent vascular proliferation and characteristic lesions.
- MCD associated with human immunodeficiency virus(HIV) infection is very similar to MCD observed in non-HIV-infected patients, except for the high prevalence of pulmonary symptoms and for the stronger association with Kaposi’s sarcoma.
- Progression to malignant lymphoma in MCD associated with HIV is frequent.
- Within a prospective cohort study of HIV-infected patients with MCD, 23% developed HHV 8-associated non-Hodgkin lymphoma.
- Localized CD:
- Poorly understood and no genetic or toxic factor has so far been identified.
- The hypothesis of a viral infection has been raised and several studies have suggested the role of human herpesvirus 8 (HHV-8), already implicated in Kaposi’s sarcoma. There are a couple of theories:
- (i) the opportunistic presence of HHV-8, favoured by immune pertubations.
- (ii) the direct pathogenic role of HHV-8, in association with dysregulation of cytokines.
- Recent studies support the latter hypothesis by demonstrating that HHV-8 is able to produce an IL-6 homologue, the interleukin reponsible for the plasmacytosis and hypergammaglobulinaemia seen in MCD.
- Tissue is the issue!
- Histopathology is characterized by distinctive follicles with expanded mantle zones of small lymphocytes forming concentric rings surrounding 1 or more atretic germinal centers.
- There is prominent vascularity of the germinal centers, often with a single prominent penetrating vessel. Another important feature is vascular proliferation between the follicles, often with perivascular hyalinization.
- The “onion-skinning” of mantle zone lymphocytes, together with the prominent central vessel, has been likened to the appearance of a lollipop
- Localized CD is treated by surgical excision which allows full recovery without relapse in almost all cases.
- Multicentric CD:
- No therapeutic consensus exists for MCD and diverse treatments (surgery/corticotherapy/chemotherapy) are used, often in combination.
- Anti-interleukin-6 antibody has also been successfully tried in the alleviation of systemic manifestations.
- The five-year survival rate in MCD is 82% and this prognosis appears to be far better than that encountered with malignant lymphomas.
Journal of Medical Case Reports 2007, 1:78
Advances in Anatomic Pathology 2009, 16: 4
Detailed Guide: Castleman Disease. American Cancer Society. 2011;http://www.cancer.org/Cancer/CastlemanDisease/DetailedGuide/.
Case Challenge #11 presented a 71 year old gentleman with lethargy, weight loss, and widespread lymphadenopathy with no palpable organomegaly. He has a polyclonal gammopathy and the following biopsy findings:
The correct answer is:
- Symptoms: serious infections, fevers, weight loss, fatigue, night sweats, and nerve damage that can cause weakness and numbness.
- Labs: frequently see anemia, hypergammaglobulinemia.
- Acts very much like lymphoma – in fact, about 20% of people with this disease eventually develop lymphoma.
- Treatment may involve steroids, surgery, chemotherapy or even radiation therapy.
Thanks for playing, case challenge #12 will be posted next week!